TY - JOUR
T1 - Autologous stem cell transplantation (ASCT) followed by consolidation chemotherapy for multiple myeloma (MM)
AU - Gojo, I.
AU - Murthy, A.
AU - Passas, A.
AU - Tricot, G.
AU - Fenton, R.
AU - Mookerjee, B.
AU - Meisenberg, B.
AU - Takebe, N.
AU - Frankel, S. R.
AU - Sarkodee-Adoo, C.
AU - Heyman, M. R.
AU - Ruehle, K.
AU - Smith, R.
AU - Cher, T.
AU - Rapoport, A.
PY - 2000/12/1
Y1 - 2000/12/1
N2 - ASCT has improved CR and survival rates for patients with MM. However, relapses occur in the majority of transplant recipients. We hypothesized that administration of 4 cycles of post-transplant (PT) consolidation chemotherapy (CC) using non cross-resistant agents might delay or prevent disease progression. Between 10/97 and 5/00 82 patients (pts) with MM received CC after autografting; 78 pts with more than 6 months of follow up were analyzed. Mobilization chemotherapy consisted of cytoxan (4.5 gm/m2) in 28 pts, cytoxan (4.5 gm/m2) plus etoposide (2 gm/ma) in 47 pts and other regimens in 3 pts. Highdose therapy consisted of BCNU (300 mg/nr, day -2) and melphalan (140 mg/m2, day -1 ). A median of 7.32 x 106/kg CD+ 34 cells were infused (range: 1.1 -38.24). CC included DCEP i DEX (40 mg/day x 4), CTX (300 mg/m2 /day x 4), VP-16 (30 mg/mVday x 4), cisplatin ( 15 mg/nv/day x 4)] by continuous infusion at 3 & 9 months PT; and DEX (40mg/day, dl-4). taxol (135 mg/m2 over 6 hr, aï) and cisplatin (75 mg/nr over 24 hrs, d3) at 6 & 12 mos PT. G-CSF (5 Hg/kg) was given with each cycle. Gemcitabine was added to the conditioning regimen and to cycles #1 and #3 for the 15 pts diagnosed > 12 mos before transplant. 14, 9, 8 and 30 pts have completed 1, 2, 3 and 4 cycles of CC. Following transplant, 29 pts (37%) were in CR, 3 pts (3.8%) were in VGPR [90% decrease in M-protein], 13 pts were in PR (16.7%) and 19 pts (24%) had SD [stable disease]. Early transplant-related mortality (< 60 days) was 7.7%. During CC, grade 3-4 myelosuppression was common; 4 patients received stem cell boosts after CC#1 for prolonged thrombocytopenia after ASCT; 1 pt died after cycle #2 due to PCP and 1 pt had a grade 4 cellulitis. After a minimum of 6 mos follow-up, 32 pts were in CR (41%), 2 pts were in VGPR (2.5%), 7 pts were in PR (9%) had 5 pts (6.4%) had SD. CC led to incremental responses in 11 pts. The median overall survival (OS) has not been reached (Kaplan Maier [KM] 2.5 yr OS = 69%) while the median KM event-free survival (EPS) was 21.1 months. Predictors of better OS and EPS included normal cytogenetic results at diagnosis and a low 2-microglobulin level; a non-IgA subtype was also marginally associated with improved EPS. Post-transplant consolidation chemotherapy is feasible and generally well-tolerated after ASCT.
AB - ASCT has improved CR and survival rates for patients with MM. However, relapses occur in the majority of transplant recipients. We hypothesized that administration of 4 cycles of post-transplant (PT) consolidation chemotherapy (CC) using non cross-resistant agents might delay or prevent disease progression. Between 10/97 and 5/00 82 patients (pts) with MM received CC after autografting; 78 pts with more than 6 months of follow up were analyzed. Mobilization chemotherapy consisted of cytoxan (4.5 gm/m2) in 28 pts, cytoxan (4.5 gm/m2) plus etoposide (2 gm/ma) in 47 pts and other regimens in 3 pts. Highdose therapy consisted of BCNU (300 mg/nr, day -2) and melphalan (140 mg/m2, day -1 ). A median of 7.32 x 106/kg CD+ 34 cells were infused (range: 1.1 -38.24). CC included DCEP i DEX (40 mg/day x 4), CTX (300 mg/m2 /day x 4), VP-16 (30 mg/mVday x 4), cisplatin ( 15 mg/nv/day x 4)] by continuous infusion at 3 & 9 months PT; and DEX (40mg/day, dl-4). taxol (135 mg/m2 over 6 hr, aï) and cisplatin (75 mg/nr over 24 hrs, d3) at 6 & 12 mos PT. G-CSF (5 Hg/kg) was given with each cycle. Gemcitabine was added to the conditioning regimen and to cycles #1 and #3 for the 15 pts diagnosed > 12 mos before transplant. 14, 9, 8 and 30 pts have completed 1, 2, 3 and 4 cycles of CC. Following transplant, 29 pts (37%) were in CR, 3 pts (3.8%) were in VGPR [90% decrease in M-protein], 13 pts were in PR (16.7%) and 19 pts (24%) had SD [stable disease]. Early transplant-related mortality (< 60 days) was 7.7%. During CC, grade 3-4 myelosuppression was common; 4 patients received stem cell boosts after CC#1 for prolonged thrombocytopenia after ASCT; 1 pt died after cycle #2 due to PCP and 1 pt had a grade 4 cellulitis. After a minimum of 6 mos follow-up, 32 pts were in CR (41%), 2 pts were in VGPR (2.5%), 7 pts were in PR (9%) had 5 pts (6.4%) had SD. CC led to incremental responses in 11 pts. The median overall survival (OS) has not been reached (Kaplan Maier [KM] 2.5 yr OS = 69%) while the median KM event-free survival (EPS) was 21.1 months. Predictors of better OS and EPS included normal cytogenetic results at diagnosis and a low 2-microglobulin level; a non-IgA subtype was also marginally associated with improved EPS. Post-transplant consolidation chemotherapy is feasible and generally well-tolerated after ASCT.
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M3 - Article
AN - SCOPUS:33748547584
VL - 96
SP - 369b
JO - Blood
JF - Blood
SN - 0006-4971
IS - 11 PART II
ER -